This research is to study genetic miscoding by metals. The rationale is based on the hypothesis that decreased fidelity of DNA synthesis by metal ions is associated with metal-induced mutagenesis and/or carcinogenesis. The aims are: 1) To determine the mechanism by which metal ions alter the fidelity of DNA synthesis in vitro; 2) to investigate whether particular metal ions bind to specific nucleotides and change the specificity of base-pairing; and 3) to analyze the relationship of this miscoding to mutations and malignancy. Genetic miscoding by metal ions will be analyzed by: 1) Measuring the frequency of non-complementary nucleotide incorporation with purified DNA polymerases and synthetic polynucleotide templates; 2) quantitating mutation rates after copying biologically active DNA by DNA polymerases in vitro; 3) studying DNA replication and DNA repair in bacterial spheroplasts and human lymphocytes; and 4) determining the amounts of trace metals associated with chromatin and DNA in normal and malignant cells.